Ion selective electrodes, hereinafter ISE's, have become a significant part of the clinical chemists' arsenal in analyzing for analytes in biological fluids. Such ISE's allow for the activity determination of ionic analytes such as Cl.sup..crclbar., Na.sup..sym., K.sup..sym. and HCO.sub.3.sup..crclbar.. These ionic analytes are useful in diagnosing, e.g., various acidosis conditions, and in the case of Cl.sup..crclbar., adrenal disease and renal failure.
For the Cl.sup..crclbar. ISE, useful electrode constructions and preparations are described in U.S. Pat. Nos. 4,214,968, issued July 29, 1980, and 4,199,411, issued Apr. 22, 1980. Such Cl.sup..crclbar. ISE is preferably prepared by forming a layer of silver on a suitable support, and thereafter converting a surface portion of the silver layer to silver chloride by treating the silver layer with a chlorochromate bath or wash. Useful examples of such a bath or wash are described in the aforesaid patents.
The most preferred construction of the Cl.sup..crclbar. ISE is one in which a thin overlayer, preferably of a cellulose ester, is formed on the silver chloride layer, as described in the aforesaid '411 patent. Although such an overlayer is not essential, it is useful in those occasional instances in which there is a potential for significant uric acid interference in the biological liquid being analyzed. That is, such overlayer has been found to be effective in reducing such interference (as well as interference from e.g., bromide ions). Uric acid, as is well known, is an endogenous purine that can be found as a natural metabolite in human body liquids.
Although such an overcoated Cl.sup..crclbar. ISE has been found to be very effective and useful, there have been a few instances in which the ISE was found to produce a large negative bias, representing a falsely reduced Cl.sup..crclbar. concentration, when used with test samples containing purines other than uric acid, e.g., hypoxanthine, allopurinol, caffeine, adenine, xanthine, theophylline and the like. These results are reported in, e.g., Clin. Chem., Vol. 30, p. 1113-1114 (1984). Such purines can occur in the patient sample from, e.g., treatment for cancer such as leukemia, when there is also acute renal failure.
Thus, prior to this invention the problem has been to provide a way of reducing the bias in the Cl.sup..crclbar. ISE that can be caused by purines other than uric acid. This has not been a facile problem to resolve, for the following reasons:
One approach was to form the AgCl layer by an alternative method different from the chlorochromate wash noted above. In such cases, the purines, noted above do not create the bias problem. However, this solution is not particularly desirable, because the use of chlorochromate oxidizing agents appears to be more effective than the noted alternatives, in reducing interference from bromide ions.
Another approach that was considered was a decrease in the permeability of the cellulose ester overcoat so as to hinder the other purines, as well as uric acid, from reaching the AgCl surface. However, this is unsatisfactory because such a decreased permeability renders the ISE less able to be operative within the desired read time, e.g., about three minutes.
For the noted reasons, the purine bias problem caused by the purines other than uric acid remained to be solved by the instant invention.